Tissue-specific adaptive levels of glucocorticoid receptor alpha mRNA and their relationship with insulin resistance.

Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified glucocorticoid receptor alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11ß-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11ß-HSD1 mRNA concentration. We also observed significantly reduced 11ß-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11ß-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRαmRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.

Influence of socio-demographic, clinical and functional factors on the severity of dementia.

Dementia is one of the most relevant illnesses due to its functional impact on the elderly. The aim of the present study was to determine the influence of socio-demographic, clinical, cognitive and functional factors on the severity of dementia in elderly individuals. One hundred six elderly individuals with a diagnosis of dementia as determined by the DSM-IV/APA participated in the study. Cognition was assessed by the mini-mental state examination (MMSE); functional performance of basic and instrumental activities of daily living (BADLs and IADLs) was assessed by the Katz index (KI), Lawton-Brody index (LBI) and Pfeffer index (PI). The severity of dementia was established through the clinical dementia rating (CDR). In order to determine the influence of factors on the degree of dementia, ordinal regression analysis was performed. Age, MMSE, KI, LBI and PI scores had statistically significant associations to the severity of dementia. However, only the age (odds ratio (OR) = 0.197; confidence interval (CI) = 0.060-0.643) and performance in IADLs (LBI: OR = 1.237, CI = 1.077-1.422; PI: OR = 0.641, CI = 0.548-0.750) were maintained in the final ordinal regression model, R(2) = 0.818. The results show that elderly individuals over 80 years of age and those with a more compromised performance in IADLs have a greater chance of exhibiting more severe degrees of dementia. These findings suggest that the ability to perform IADLs may be an important variable in differentiating degrees of the severity of dementia.

Applicability of real-time PCR methodology in the neonatal detection of Turner syndrome.

Turner syndrome (TS) is the complete or partial loss of the second sex chromosome, occurring in 1:5 000 girls. Early recognition allows appropriate therapy for short stature and puberty. Neonatal diagnosis of TS permits detection of associated malformations, minimizing sequels. Aiming to develop a molecular method for the diagnosis of TS we employed blood samples stored on filter paper. We evaluated 78 female controls, 25 TS girls with 45,X karyotype, and 32 TS patients with other karyotypes. After DNA extraction, samples were submitted to real-time PCR, using primers and probes directed to the study gene ARSE and to the control gene GAPDH. A ROC curve established the ARSE:GAPDH ratio with a cutoff value of 0.7. Low ARSE:GAPDH ratio of <0.7 was present in 100% of 45,X TS patients. This cutoff value presented a sensitivity of 100% and a specificity of 100% in detecting 45,X TS patients with a positive predictive value of 100% and a negative predictive value of 100%. The same cutoff value was able to identify only 56% of TS with other karyotypes, in which we observed a mean (SD) ARSE:GAPDH ratio=0.66 (0.2); and the interquartile range=0.4-0.8. Determination of ARSE:GAPDH ratio is a fast, sensitive, and specific method, with viable cost and feasible automation, which makes it potentially applicable in neonatal screening programs for the diagnosis of Turner syndrome 45,X.

First two years' response to growth hormone treatment in very young preterm small for gestational age children.

BACKGROUND: Growth hormone (GH) is a therapeutic option for small for gestational age (SGA) children without spontaneous catch-up. There are few reports on preterm SGA children. Prematurity is an additional risk factor for adult short stature. AIM: To describe GH efficacy in preterm SGA patients. METHODS: Twenty-five preterm SGA patients, 2-4 years old, treated with GH 0.066 mg/kg/day, were compared with 14 age-matched preterm SGA historical controls. Height, weight, IGF-I, IGFBP-3, fasting glucose and insulin were measured every 6 months. RESULTS: At start of GH treatment, mean height and weight were -2.4 and -2.4 SDS, respectively. There was a significant increment in height SDS of 1.3 and 2.1 during the 1st and the 2nd year of GH therapy, respectively. There was no significant difference between the progression of chronological and bone ages. A significant increase in IGF-I, IGFBP-3 and molar ratio was observed during GH therapy. There was no difference in glucose, insulin or HOMA-IR index. CONCLUSION: We showed for the first time that the height increment of preterm SGA with GH treatment is similar to that described in other studies with term SGA patients. Therefore, short-term GH treatment in a subset of preterm SGA patients between 2-4 years of age was able to promote adequate growth recovery with no excessive bone age acceleration or adverse effects on carbohydrate metabolism.

Impact of prolonged physical training on the pituitary glucocorticoid sensitivity determined by very low dose intravenous dexamethasone suppression test.

The activity of the hypothalamic-pituitary-adrenal axis is usually modulated by several stress factors, including exercise. Different responses are induced by physical training according to duration and intensity of exercise. During prolonged training, cortisol remains normal or decreased as a consequence of altered cortisol secretion, metabolism and excretion, and possibly by changes in glucocorticoid sensitivity. The aim of this study was to evaluate the impact of prolonged physical training on the glucocorticoid sensitivity. Eighteen cadets of the Air Force Academy, mean (SD) age: 18.7 (1.0) years, underwent an intensive 6-week preparatory training-period considered adequate by inducing significant changes on body composition measured by bioelectrical impedance. Measurement of individual's pituitary glucocorticoid sensitivity was done by an intravenous very low dose dexamethasone suppression test (20 microg/m (2)) that was performed before and after the training period. Cortisol levels were obtained at basal condition and 120 minutes after the dexamethasone infusion. Basal cortisol showed a significant decrease after prolonged training. The percent cortisol suppression after dexamethasone tended to be lower after the training period. Overall, our data suggest that prolonged physical training is able to reduce glucocorticoid sensitivity, which can have a beneficial impact in chronic stress conditions.

Avaliação das atividades de vida diária de idosos com diferentes níveis de demência / Evaluation of the activities of daily living of elderly people with different levels of dementia

OBJETIVOS: Comparar o desempenho de idosos com diferentes níveis de gravidade de demência em questionários de atividades básicas de vida diária (ABVDs) e atividades instrumentais de vida diária (AIVDs). Verificar se existe correlação entre os questionários de AIVDs aplicados. METODOLOGIA: Foram aleatorizados 90 idosos (75,46 ± 7,66 anos) atendidos no Centro de Referência do Idoso-MG, com diagnóstico clínico de demência (DSM-IV/APA) e classificados quanto ao nível de gravidade da demência (Clinical Dementia Rating). As ABVDs foram avaliadas pelo índice de Katz, e as AIVDs, pelo índice de Lawton-Brody e de Pfeffer. Os testes de Kruskal-Wallis e de Mann-Whitney foram utilizados para verificar o desempenho dos idosos nas ABVDs, e a correlação de Spearman, para investigar a relação entre os instrumentos de AIVDs (alfa< 0,05). RESULTADOS: Foram encontradas diferenças estatisticamente significativas entre o desempenho dos idosos com diferentes níveis de gravidade de demência avaliados pelos instrumentos de ABVDs e AIVDs (p< 0,001). Os questionários de AIVDs apresentaram correlação significativa na amostra total (p< 0,0001; r= -0,818), nos grupos com demência leve (p= 0,007; r= -0,530) e grave (p< 0,0001; r= -0,723). CONCLUSÃO: A gravidade do processo demencial interferiu no desempenho dos idosos nas atividades básicas e instrumentais de vida diária. As AIVDs foram mais comprometidas nos estágios iniciais das demências, e as ABVDs, nos estágios mais avançados. Os questionários de AIVDs utilizados, apesar de sua particularidade estrutural, parecem medir um construto comum. A variabilidade do quadro clínico nos indivíduos com demência moderada pode explicar a ausência de correlação dos questionários usados nesse grupo específico.

OBJECTIVE: To compare the performance of elderly people with different levels of severity of dementia using questionnaires on basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). Also, to verify whether there were any association between the IADL questionnaires applied. METHOD: Ninety elderly people, aged 75.46 ± 7.66 years with a clinical diagnosis of dementia (DSM-IV/APA) who were seen at the Minas Gerais Reference Center for the Elderly, were randomized selected and classified according to the level of severity of their dementia (Clinical Dementia Rating). Their BADLs were assessed using the Katz Index and their IADLs by the Lawton-Brody and Pfeffer indexes. The Kruskal-Wallis and Mann-Whitney tests were used in order to investigate the elderly people's performance regarding BADLs, while the Spearman correlation was used to investigate the relationships among the IADL (alpha< 0.05). RESULTS: Statistically significant differences in performance were found between the elderly people with different levels of severity of dementia, as assessed by the BADL and IADL questionnaires (p< 0.001). The IADL questionnaires presented significant correlation for the total sample (p< 0.0001; r = -0.818) as well as for the groups with mild dementia (p= 0.007; r = -0.530) and severe dementia (p< 0.0001; r = -0.723). CONCLUSION: The severity of the dementia process interfered with the elderly people's performance of the elderly in BADLs and IADLs. The IADLs were more affected in the early stages of dementia whereas the BADLs were more affected in the more advanced stages. Despite structural particularities, the IADL questionnaires utilized seemed to be measuring a common construct. The variability in the clinical condition of the individuals with moderate dementia may be an explanation for the lack of correlation between the questionnaires in this specific group.

A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita.

Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely.

Estudo da relação entre o comprimento da banda iliotibial e o desalinhamento pélvico / Study on the relationship between iliotibial band length and pelvic misalignment

CONTEXTUALIZAÇÃO: Desalinhamentos pélvicos, como a inclinação lateral, ocasionam diferentes disfunções e queixas de dor. Na literatura, são apontados diversos fatores associados à inclinação lateral da pelve, sendo um deles o comprimento da banda iliotibial. OBJETIVO: Verificar a existência de correlação entre o comprimento da banda iliotibial e o desalinhamento pélvico no plano frontal. MÉTODO: Trinta e dois indivíduos (22,5 ± 2,6 anos) de ambos os sexos, assintomáticos, sem diferença no comprimento dos membros inferiores e sem torção pélvica, foram incluídos no estudo. Para a medida do comprimento da banda iliotibial, utilizou-se o teste de Ober modificado, um nível pélvico e um inclinômetro e, para determinar o desalinhamento pélvico no plano frontal, foram utilizadas medidas de estruturas pélvicas obtidas por um antropômetro com o indivíduo posicionado em um instrumento de suporte de padronização. O Coeficiente de correlação de Pearson foi utilizado para investigar a associação entre as variáveis analisadas: o desalinhamento pélvico no plano frontal, determinado pela diferença da altura da espinha ilíaca ântero-superior mais elevada menos a altura da mais baixa e o comprimento da banda iliotibial, determinado pela diferença entre o comprimento da banda iliotibial correspondente à espinha ilíaca ântero-superior mais elevada menos o comprimento da mesma estrutura correspondente a espinha mais baixa. RESULTADOS: Não foi encontrada correlação estatisticamente significativa entre as variáveis analisadas (r=0,12, p=0,53). CONCLUSÃO: Os achados do presente estudo indicam que o comprimento da banda iliotibial, isoladamente, parece não influenciar o alinhamento pélvico no plano frontal. Entretanto, outros fatores podem estar envolvidos e precisam ser identificados.

BACKGROUND: Pelvic misalignments such as lateral pelvic tilt may lead to dysfunctions and pain complaints. Studies in the literature have indicated several factors associated with lateral pelvic tilt, and one of these is the length of the iliotibial band. OBJECTIVE: Investigate the presence of an association between iliotibial band length and frontal plane pelvic tilt. METHOD: Thirty-two asymptomatic individuals of both sexes (22.5 ± 2.6 years), without leg-length differences or pelvic torsion, were included in the study. The modified Ober test, performed with a pelvic level and an inclinometer, was used to assess the iliotibial band length. To determine the pelvic misalignment in the frontal plane, the individual was positioned on standard support equipment and pelvic structure measurements were obtained using an anthropometer. Pearson's correlation coefficient was utilized to determine the degree of association between pelvic misalignment in the frontal plane (established as the difference in height between higher and lower anterosuperior iliac spines) and the length of the iliotibial band (established as the difference in iliotibial band lengths corresponding to the higher and lower anterosuperior iliac spines). RESULTS: No statistically significant correlations were found between the variables analyzed (r=0.12; p=0.53). CONCLUSION: The present findings indicate that iliotibial band length alone does not appear to influence frontal plane pelvic alignment. Other factors may be involved and these still need to be identified.

Transdermal estradiol priming during clonidine stimulation test in non-growth hormone deficient children with short stature: a pilot study.

The diagnosis of growth hormone (GH) deficiency is strongly influenced by age, body mass index and presence of gonadal steroids. Priming with oral estradiol (E2) is one possible way to overcome the impact of variable levels of sex steroids. We describe the effects of transdermal estradiol (E2-t) priming on GH response after clonidine stimulation in prepubertal children with familial short stature (group 1, n = 12) or constitutional growth delay (group 2, n = 22). All patients underwent a clonidine test (0.1 mg/m2, p.o.) followed by a clonidine plus E2-t test (50 microg/day) with a 7-day interval. Before E2-t, basal GH and insulin-like growth factor-I (IGF-I) values were similar in the two groups. After E2-t priming, basal GH was significantly higher only in group 2. When compared with group 1, patients from group 2 had a significant increase of GH peak response when submitted to E2-t. The number of patients in both groups with adequate GH peak response was higher after E2-t priming. We conclude that E2-t priming is able to increase GH peak response after clonidine stimulation and also improves the accuracy of the clonidine test in the diagnosis of GH deficiency. Compared to oral administration, E2-t delivery can prevent liver toxicity, providing a more physiological mechanism of GH secretion.

Treinamento fisico e destreinamento em hemiplegicos cronicos: impacto na qualidade de vida / Physical training and detraining among chronic stroke surviors: impact on quality of life

A alta incidencia de Acidentes Vasculares Encefalicos (AVE), a significativa taxa de sobrevida e a permanencia de incapacidades pos-AVE justificam a importancia de avaliar a qualidade de vida desses pacientes a (QV). Objetivo: avaliar os ganhos na QV de hemiple cronicos comunitarios apos a realizacao de um programa de treinamento fisico em grupo e apontar os dominios de QV significativamente responsaveis por tais ganhos. Metodo: 30 individuos de ambos os sexos realizaram 30 sessoes de um programa de treinamento fisico envolvendo atividades aerobicas associadas a exercicios de musculacao e foram avaliados antes e imediatamente apos a intervencao. Desses, 22(57,66+=11,95 anos0 foram reavaliados apos um ano do termino das atividades (follow-up). A QV foi investigada nas tres avaliacoes mediante o Perfil de Saude de Nottingham, questionario com seis dominios de QV...